US2773900A - Substituted aryl amino alkyl ethers - Google Patents
Substituted aryl amino alkyl ethers Download PDFInfo
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- US2773900A US2773900A US467635A US46763554A US2773900A US 2773900 A US2773900 A US 2773900A US 467635 A US467635 A US 467635A US 46763554 A US46763554 A US 46763554A US 2773900 A US2773900 A US 2773900A
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- US
- United States
- Prior art keywords
- ether
- acid
- phenylphenyl
- substituted aryl
- alkyl ethers
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 125000003107 substituted aryl group Chemical group 0.000 title 1
- 229940066768 systemic antihistamines aminoalkyl ethers Drugs 0.000 title 1
- 239000002253 acid Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- -1 alkyl radicals Chemical class 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- SZFRTHYPBFFRMI-UHFFFAOYSA-N 2-(2,4-dichloro-6-phenylphenoxy)-N,N-dimethylethanamine Chemical compound CN(C)CCOC1=C(C=C(C=C1C1=CC=CC=C1)Cl)Cl SZFRTHYPBFFRMI-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical compound NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 3
- AFXPPGXJWHJULD-UHFFFAOYSA-N 2-Hydroxy-3,5-dichlorobiphenyl Chemical compound OC1=C(Cl)C=C(Cl)C=C1C1=CC=CC=C1 AFXPPGXJWHJULD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229910052801 chlorine Chemical group 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FUJSJWRORKKPAI-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1Cl FUJSJWRORKKPAI-UHFFFAOYSA-N 0.000 description 1
- GTEXIOINCJRBIO-UHFFFAOYSA-N 2-[2-(dimethylamino)ethoxy]-n,n-dimethylethanamine Chemical compound CN(C)CCOCCN(C)C GTEXIOINCJRBIO-UHFFFAOYSA-N 0.000 description 1
- XBILVINOJVKEHG-UHFFFAOYSA-N 2-chloro-6-phenylphenol Chemical compound OC1=C(Cl)C=CC=C1C1=CC=CC=C1 XBILVINOJVKEHG-UHFFFAOYSA-N 0.000 description 1
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
Definitions
- the compounds of this invention are pharmaceutically useful as drug-prolonging agents, for example, in prolonging and potentiating the action of barbiturates and analgesics.
- the above novel compounds can be incorporated into tablets, capsules, suspensions, emulsions, solutions, and other like pharmaceutical forms, using the appropriate pharmaceutical extending media as known to the art.
- the compounds exhibit their usefulness as drug-prolonging agents when administered orally or parenterally in conjunction with the drug whose action is to be prolonged.
- R1 and Re can be the same or different lower alkyl radicals such as methyl, ethyl, propyl, isopropyl, and the like.
- acids which can form nontoxic, pharmaceutically useful acid addition salts with the bases of the above formula are the following: hydrochloric acid, hydrobromic acid, sulfuric acid, ascorbic acid, phosphoric acid, tartaric acid, maleic acid, succinic acid, oxalic acid, and the like.
- novel amino alkyl phenyl ethers provided by my invention are prepared as follows: An alkali metal salt of the substituted phenol is prepared in a suitable solvent. To this stirred mixture is added a dialkyl-fi-haloethyl amine in the form of its free base. The reaction mixture is heated for several hours, and is then filtered to remove inorganic salts. The resulting amino alkyl phenyl ether is contained in the filtrate and is isolated and purified by conventional means, such including extraction into dilute acid, neutralization of the acid extract, extraction back into an organic phase, distillation of the free base, and preparation therefrom of a crystalline acid addition salt.
- I'hel-eoma bined, acid. extracts were made ba sie' and theibaseiiusoluble material, comprising 2,4;diehloro6-ghenylphenyl; di-i ethyl-a'minoethyl ether was extracted into .diethyl ether.
- a base represented by the following formula 3 A base represented by the fol1owing,formula References Cited in the file ofl this patent I UNITED 'STATESPATENTS 2,187,723 2,217,660 Alquist et a1. Oct. 15, 1940 Binkleyet a1.” Mar.- 1' 1955 Alquist et a1. Jan. 23, 1940
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
United States Patent SUBSTITUTED ARYL AlVflNO ALKY L ETHERS Jack Mills, Glenns Valley, Ind., assignor to Eli Lilly and Company, Indianapolis, 11111., a corporation of Indiana No Drawing. Application November 8, 1954, Serial No. 467,635
4 Claims. (Cl. 260570.7)
m-Q-o-om-cm-r/ I Rs 01 in which R1 and R2 represent lower alkyl groups and R3 is a hydrogen or a chlorine atom. The compounds of this invention are pharmaceutically useful as drug-prolonging agents, for example, in prolonging and potentiating the action of barbiturates and analgesics. For such purposes the above novel compounds can be incorporated into tablets, capsules, suspensions, emulsions, solutions, and other like pharmaceutical forms, using the appropriate pharmaceutical extending media as known to the art. The compounds exhibit their usefulness as drug-prolonging agents when administered orally or parenterally in conjunction with the drug whose action is to be prolonged.
In the above formula, R1 and Re can be the same or different lower alkyl radicals such as methyl, ethyl, propyl, isopropyl, and the like. Among the acids which can form nontoxic, pharmaceutically useful acid addition salts with the bases of the above formula are the following: hydrochloric acid, hydrobromic acid, sulfuric acid, ascorbic acid, phosphoric acid, tartaric acid, maleic acid, succinic acid, oxalic acid, and the like.
Broadly, the novel amino alkyl phenyl ethers provided by my invention are prepared as follows: An alkali metal salt of the substituted phenol is prepared in a suitable solvent. To this stirred mixture is added a dialkyl-fi-haloethyl amine in the form of its free base. The reaction mixture is heated for several hours, and is then filtered to remove inorganic salts. The resulting amino alkyl phenyl ether is contained in the filtrate and is isolated and purified by conventional means, such including extraction into dilute acid, neutralization of the acid extract, extraction back into an organic phase, distillation of the free base, and preparation therefrom of a crystalline acid addition salt.
My invention is further illustrated by the following specific examples:
EXAMPLE 1 Preparation of 2-chloro-6-phenylphenyl dimethylaminoethyl ether hydrochloride 2.5 g. of sodium metal were reacted with 200 m1. of ethanol to form a solution of sodium ethoxide. 20.5 g. of 2-chloro-6-phenylphenol were added with stirring to 2,773,900 vPatented Dec. 11, 1956 this solution, yielding the sodium salt of the phenol. 18
- g. of dimethyl-p-chloroethylamine were next added to the reaction mixture. After addition of the amine was complete, the reaction mixture was heated to refluxing temperature for about 12 hours, thus forming 2-chloro-6- phenylphenyl dimethylaminoethy-l ether. The reaction mixture was cooled and was filtered to remove inorganic salts. the alcohol. The organic layer which separated was shaken with dilute hydrochloric acid, the 2-chloro-6-phenylphenyl dimethylaminoethyl ether being extracted into theaqueous acid layer as the soluble hydrochloride salt.
ether solutions of the said base, there were obtained the corresponding maleate and phosphate salts, respectively. Likewise, other salts such as the tartrate, ascorbate and The acid extract was then made basic with aqueous sodium hydroxide solution and the amino-ether which separated'from solution was extracted into diethyl ether. The
ether layer was washed with water, was dried with anhydrous magnesium sulfate, and the ether was evaporated off. The oily residue comprising 2chl0r06-phenylphenyl dimethylaminoethyl etherwas distilled. The distillate was dissolved in ether and HCl gas bubbled into the solution in order to prepare the hydrochloride salt of 2-chloro- 6-phenylphenyl diinethylaminoethyl ether. After recrys tallization, this hydrochloride salt melted at about.
Other salts of 2-chloro-6-phenylphenyl dimethylaminoethyl ether are made by dissolving the free base in ether and adding an equivalent weight of the desired acid thereto. Thus, by addition of maleic or phosphoric acid to Preparation of 2,4-dich[moo-phenylphenyl dimezhylaminoethyl ether A toluene solution containing 23.9 g. of 2,4-dichloro- 6-phenylphenol was added to a refluxing toluene suspension of 5.2 g. of sodium hydride, thus forming the sodium salt of the phenol. Rcfluxing was continued for one hour after addition of the phenol was complete. An ether solution containing 21.6 g. of dimethyl-fl-chloroethylamine was then added dropwise to the reaction mixture, and heating at refluxing temperature was continued overnight. By this reaction 2,4-dichloro-6-phenylphen yl dimethylaminoethyl ether was formed. The reaction mixture was poured over ice and 500 ml. of diethyl ether were added thereto. The organic layer was separated and then extracted twice with 200 ml. portions of 10 percent hydrochloric acid, the amino-ether being extracted into the acidic layer at this point. The acidic extracts were combined, were made basic with aqueous sodium hydroxide, were extracted with two 500 ml. portions of ether, and the amino-ether extracted back into diethyl ether. The combined ether extracts, which now contained the free base of 2,4-dichloro-6-phenylphenyl dimethylaminoethyl ether were dried and filtered, and the filtrate was distilled. 2,4-dichloro-6-phenylphenyl dimethylaminoethyl ether distilled at about 138-l56 C. at a pressure of about 0.4 mm. of mercury. The yield was 22 g.
The hydrochloride salt of 2,4-dichloro-6-phenylphenyl dimethylaminoethyl ether was prepared and purified by the procedures disclosed in Example 1. It melted at about 186-187 C. Analysis showed the presence of,
About 1 1. of diethyl ether was added to dilute EXAMPLE 3 n r Preparation of 2,4'dichl0ro-6-phenylphenyl diethylaminoethyl ether A solution of sodiumethoxide was; preparedibjt, dis
solving 2.5 g. of sodium in 200 ml. of ethanol; 26, 3 g.. of 2,4-dichloro-6-phenylphenol were added dropwise 0-- this solution, thus formingv the sodium saltpof theghenoL. To the resulting solution'were added 23. g. of diethyl-B chloroethylamine and the mixture was heated at refluxing temperature overnight. The reaction mixture containing the desired 2,4-dichloro-6-phenylphenyl diethyglaminq. ethyl ether was poured, over. ice, andthe aminQ-etherwas extractedinto diethyl ether. The etherelayer -wasithenextracted. twice with dilute. hydrochloric, acid. I'hel-eoma bined, acid. extracts were made ba sie' and theibaseiiusoluble material, comprising 2,4;diehloro6-ghenylphenyl; di-i ethyl-a'minoethyl ether was extracted into .diethyl ether.
The, ether layer was washediwith Water, was. dried; over anhydrous magnesium sulfate, and was .filtered: to-remoye.
th'edrying agent, Ttie solventwasl euagoratedintvacuo, .andithe residue of 2-, 4.-di'chloro.-6+phenylphenyl diethylar'ninoethyl ether wassdistille'd- The fraction. boiling betweeuabout 150-162" C. at a pressureof about; 1,0
of, mercury was collected. measure waseonyerted to the. hydrobroinide salt by t hernethqd 0f; Exan igleel. The resulting crystallinematerial, 2-, 4dichloro-6-phenylphenyl diethylaminoethyl' ether hydrolf romide melted at, about 131132 C. Analysis shbw ed'the rpresence of.
18.82 percent bromine as comparedwitl1 thi6aleulated value of 19.08. percent.- r
I claim; v
1; A pharm acologically active comfloundof theclasst consisting of a base and itsfnontoxie pharmaceutically usefullacid addition salts", said base beingrepresented by I the formula in which R1 and R2 represent lower alkyl groups and Rs i'scliosen from" the clas'scon'si'sting 'of' a'hyd'r'oge'n atom" and a chlorine atom.
2. A base represented by the following formula 3. A base represented by the fol1owing,formula References Cited in the file ofl this patent I UNITED 'STATESPATENTS 2,187,723 2,217,660 Alquist et a1. Oct. 15, 1940 Binkleyet a1." Mar.- 1' 1955 Alquist et a1. Jan. 23, 1940
Claims (1)
1. A PHARMACOLOGICALLY ACTIVE COMPOUND OF THE CLASS CONSISTING OF A BASE AND ITS NONTOXIC PHARMACEUTICALLY USEFUL ACID ADDITION SALTS, SAID BASE BEING REPRESENTED BY THE FORMULA
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US467635A US2773900A (en) | 1954-11-08 | 1954-11-08 | Substituted aryl amino alkyl ethers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US467635A US2773900A (en) | 1954-11-08 | 1954-11-08 | Substituted aryl amino alkyl ethers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2773900A true US2773900A (en) | 1956-12-11 |
Family
ID=23856490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US467635A Expired - Lifetime US2773900A (en) | 1954-11-08 | 1954-11-08 | Substituted aryl amino alkyl ethers |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2773900A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2879293A (en) * | 1957-02-19 | 1959-03-24 | Hoffmann La Roche | Benzylamine derivatives |
| US3139430A (en) * | 1960-12-20 | 1964-06-30 | Merck & Co Inc | 2-dialkylaminoalkoxy-6-substituted naphthalenes useful as new anticholesteremic agents |
| US3178420A (en) * | 1959-06-25 | 1965-04-13 | Richardson Merrell Inc | Amino-2-hydroxy-1-propoxy benzal derivatives of fluorene and xanthene |
| US3213140A (en) * | 1960-09-06 | 1965-10-19 | Lilly Co Eli | 2-phenyl-4, 6-dichlorophenoxyethylamine and salts thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2170324A (en) * | 1937-09-15 | 1939-08-22 | Hanna Samuel Orr | Dust evacuating device |
| US2187723A (en) * | 1938-07-27 | 1940-01-23 | Dow Chemical Co | Primary xenoxy-alkyl amines |
| US2217660A (en) * | 1938-07-27 | 1940-10-15 | Dow Chemical Co | Secondary xenoxy-alkyl amines |
-
1954
- 1954-11-08 US US467635A patent/US2773900A/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2170324A (en) * | 1937-09-15 | 1939-08-22 | Hanna Samuel Orr | Dust evacuating device |
| US2187723A (en) * | 1938-07-27 | 1940-01-23 | Dow Chemical Co | Primary xenoxy-alkyl amines |
| US2217660A (en) * | 1938-07-27 | 1940-10-15 | Dow Chemical Co | Secondary xenoxy-alkyl amines |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2879293A (en) * | 1957-02-19 | 1959-03-24 | Hoffmann La Roche | Benzylamine derivatives |
| US3178420A (en) * | 1959-06-25 | 1965-04-13 | Richardson Merrell Inc | Amino-2-hydroxy-1-propoxy benzal derivatives of fluorene and xanthene |
| US3213140A (en) * | 1960-09-06 | 1965-10-19 | Lilly Co Eli | 2-phenyl-4, 6-dichlorophenoxyethylamine and salts thereof |
| US3139430A (en) * | 1960-12-20 | 1964-06-30 | Merck & Co Inc | 2-dialkylaminoalkoxy-6-substituted naphthalenes useful as new anticholesteremic agents |
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